Pharmacogenomics: The Science of Personalizing Drugs Based On DNA

The Medical Futurist 27 November 2018

Individuals share about 99.97 percent of their DNA and only the remaining 0.03 percent is responsible for the differences in skin, hair or eye color, height, shoe size or sunspots. Scientists discovered somewhat recently that our bodies also metabolize drugs differently so it would make sense to prescribe medications based on the knowledge hidden in our DNA. In some cases, physicians already do that. Here’s what you need to know about pharmacogenomics and the future of prescription drugs.

It’s all in your genes

Why do some people eat creamy French cakes all the time, only do sports when they have to run after the bus and still remain in shape? How come when others eat some chips, the next day they’ll gain two pounds? What exactly is the reason for some people not being able to drink coffee after 6 pm otherwise they will be up all night; and why do others have some double espresso at 11 pm and sleep around midnight as if nothing happened?

The response is all in your genes. Well, more precisely how your organism’s metabolic processes work, which are determined by the double spiral. Genetics and genomics aim to uncover the most hidden secrets of our bodies, and how the human organism might respond to environmental factors. Two specific strands concentrate on metabolic issues: nutrigenomics and pharmacogenomics. The first one deals with food issues and the latter with the drug response of our bodies due to the genetic code. Generally, it argues that despite general sentiments, medications do not have the same effect on people.

Source: www.europeanpharmaceuticalreview.com

A powerful combination: the science of drugs and genetics

Pharmacogenomics is viewed as a critical area for improving drug therapy and prescriptions in the future. The relatively new science started to challenge the widely held view among doctors, pharmacists and other experts that drugs have pretty much the same effect on everyone. Recent studies show that people metabolize medication on a wide scale and have considerable variations in side effects based on their DNA. In the case of several drugs, scientists could already pinpoint gene variations which make the patient more sensitive to a standard dose and others which cause a faster metabolic response to a drug than normally. If someone with such DNA variations received the standard dose that works for the general population, they would have side effects that might require hospitalization.

The Personalized Medicine Coalition (PMC) has been facilitating the use of pharmacogenomics since 2004. According to the organization, we already know of more than 50 million DNA variations, thousands of which are associated with specific drugs and diseases. More than a 100 drugs are already available whose labels include pharmacogenomic information based on studies that have found associations between genetic aspects and sensitivity to that particular drug. It was high time as studies show that medications are ineffective for about 40 percent of patients with asthma, depression, and diabetes. It has nothing to do with the quality of the drug or the physician’s treatment plan, but the fact that we are all genetically unique.

Source: www.genome.gov

The right dose against blood clotting

Let’s look at the drug called Warfarin or as also commonly known Coumadin, a blood thinner. It is an anticoagulant that works by decreasing the clotting ability of the blood. It’s widely prescribed to prevent blood clots in people with conditions such as atrial fibrillation, deep vein thrombosis, or pulmonary embolism. However, its dosing is very tricky. If the doctor prescribes too little, blood clots might take shape in spite of the medical efforts. On the other hand, if the doctor prescribes too much, it can cause excess bleeding.

Two genes are known to influence warfarin’s effectiveness. One, called CYP2C9, deactivates warfarin. The other, VKORC1, activates vitamin K, which is essential for blood clotting. Variations in these genes affect how a person responds to warfarin. Thus, dosing formulas have been developed to incorporate a person’s genetic profile, along with their clinical characteristics, to better predict the warfarin dose that a person might need. Some are skeptical about genotyping and dosing medications based on it, but some expressly recommend genetic testing before any prescription of, e.g., Warfarin takes place. Nevertheless, in 2007, the FDA revised the label on the blood-thinning drug to explain that a person’s genetic makeup might influence response to the medication. Although the data are still evolving, early evidence suggests that genetic testing in advance of prescribing warfarin helps patients avoid severe and possibly fatal adverse effects.

For the more economical beings amongst us, data also suggest that the management of dosing of warfarin based on pharmacogenomic outcomes can eliminate costs associated with hospitalizations for bleeding or thromboembolism. The Mayo Clinic and the pharmacy benefits manager Medco put the model to the test in a 3,600-subject prospective study. Hospitalization rates for heart patients were reduced by about 30 percent when genetic information was available to doctors prescribing the drug.

I reviewed the myDNA Medication test before, which found that if I have to take Codeine (an opiate used to treat pain); fluvoxamine (used to treat obsessive-compulsive disorder); or simvastatin (used to lower cholesterol), I will have major side effects from cardiomyopathy to liver problems. Recently, I had my Dante Labs whole genome sequencing experience, and as part of it, I received a 163-pages-long report with a special section devoted to pharmacogenomics. Among others, I was tested for Warfarin, and it turned out I have a slight resistance towards that. Nevertheless, I received information about how my body metabolizes more than a hundred drugs, which is incredibly useful. For example, my cholesterol level is usually higher as the reference value. However, I would definitely have severe side effects if I took prescription pills for high levels of cholesterol. That’s another indication for risk for cardiomyopathy, for example.

The future might hold entirely personalized drugs

On the individual level, having a pharmacogenomic test could eventually help patients avoid adverse effects of medication and support physicians in working out the most appropriate treatment with the most suitable drug for their patients. This practice will represent another element which will gradually bring medicine from a reactive to a preventive discipline.

Although for doing so, doctors should master the skills of making sense of genetic findings to guide patients in the sea of genetic data and recommendations. As interpretation of genetic results might be the trickiest part, introducing genomic medicine in the current medical school curriculum might help – alongside with decision-making in the era of precision medicine.

Besides improving how existing drugs are used, genome research will lead to the development of better drugs. The goal is to produce new drugs that are highly effective and do not cause serious side effects. The pharmaceutical sector seems to have accepted the challenge. According to the already cited report of the PMC, biopharmaceutical industry players estimate that 42 percent of all compounds and 73 percent of oncology compounds in the pipeline have the potential to be personalized medicines. Over the past five years, biopharmaceutical companies nearly doubled their R&D investment in personalized medicines, while biopharmaceutical researchers predict a 69 percent increase in the number of personalized medicines in development over the next five years.

If the estimates are accurate, pharmaceutical companies will mostly produce personalized medicines within a decade. Bearing all these pieces of information in mind, the future scenario where you go to your physician, and after an examination, the doctor 3D prints the appropriate medication for you based on your pharmacogenomic parameters doesn’t sound that futuristic after all.